Systems and methods for detecting evoked compound action potential (ecap) features in response to neurostimulation

ABSTRACT

Systems and methods are disclosed for conducting spinal cord stimulation or other neurostimulation and sensing evoked compound action potential (ECAP) signals. The sensed signals may be processed to isolate ECAP features from noise and/or interfering signals. The isolated ECAP features may be used to control neurostimulation therapy for the patient and/or guide an implant procedure.

RELATED APPLICATION(S)

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 63/285,723, filed Dec. 3, 2021, entitled “SYSTEMSAND METHODS FOR DETECTING EVOKED COMPOUND ACTION POTENTIAL (ECAP)FEATURES IN RESPONSE TO NEUROSTIMULATION,” which is incorporated hereinby reference in its entirety.

TECHNICAL FIELD

The present application generally relates to treating pain throughelectrical stimulation, and more particularly to sensing and detectingresponsive signals, such as evoked compound action potentials (ECAPs),in response to the electrical stimulation.

BACKGROUND OF THE INVENTION

Implantable medical devices are used for a wide variety of medicalconditions. For example, a number of implantable medical devices havebeen commercially distributed that allow electrical pulses or signals tobe controllably delivered to targeted tissue or nerves afterimplantation of the respective device within a patient. Such implantablemedical devices may be used for cardiac pace making, cardiac rhythmmanagement, treatments for congestive heart failure, implanteddefibrillators, and neurostimulation. Neurostimulation encompasses awide range of applications, such as for example, treatment of chronicpain, treatment of motor disorders, treatment of incontinence and othersacral nerve related disorders, reduction of epileptic seizures, andtreatment of depression. Neurostimulation in the form of spinal cordstimulation (SCS), for example, has been used as a treatment for chronicpain for a number of years. SCS is often used to alleviate pain afterfailed surgery, pain due to neuropathies, or pain due to inadequateblood flow. In accordance with SCS therapy, non-nociceptive fibers arestimulated to alleviate pain symptoms in cases of chronic pain.

Implantable electrical stimulation devices generally include animplanted pulse generator that generates electrical pulses or signalsthat are transmitted to targeted tissue or nerves through a therapydelivery element, such as a lead with an electrode array. In the case ofSCS, an electrode array present on a distal end of a lead may beimplanted so as to be disposed within the epidural space for delivery ofthe electrical stimulation. A pulse generator coupled to a proximal endof the lead may thus be enabled to apply neural stimuli to the dorsalcolumn in order to give rise to a compound action potential (CAP). Thedorsal column contains the afferent A-beta (Aβ) fibers to mediatesensations of touch, vibration, and pressure from the skin, whereby onesof the Aβ fibers may be therapeutically recruited by the neural stimuliprovided through the electrode array by the pulse generator.

According to conventional SCS, stimulation pulses are provided to neuraltissue of the dorsal column in a regular pattern with each pulse havinga predetermined amplitude (e.g., current intensity) and being separatedby a fixed inter-pulse interval that defines a stimulation frequencyconfigured for inducing a tingling sensation (known medically asparesthesia) in the patient. For example, stimulation of the Aβ fibersmay induce paresthesia and therefore may provide the mechanism of actionfor traditional tonic SCS to mask the pain. Although the paresthesia canbe uncomfortable or even painful in patients, the paresthesia is oftensubstantially more tolerable than the pain otherwise experienced by thepatients.

A more recent approach to pain management through SCS is to usehigh-frequency SCS (HFSCS) to provide paresthesia-free therapy. HFSCStypically includes pulses at frequencies between 1500 Hz and 10,000 Hzalthough even higher frequencies could be used. In accordance withHFSCS, high-frequency electrical pulses are delivered at a currentintensity below the paresthesia threshold. For example, HFSCSstimulation regimens implementing a stimulation frequency of up to 10kHz have been found to be effective in providing pain relief withouteliciting paresthesia (see e.g., Arie J E, Mei L, Carlson K W, and ShilsJ L, “High frequency stimulation of dorsal column axons: potentialunderlying mechanism of paresthesia-free neuropathic pain”, Poster atInternational Neuromodulation Society Conference, 2015; and AdnanAl-Kaisy, MD, Jean-Pierre Van Buyten, MD, Iris Smet, MD, StefanoPalmisani, MD, David Pang, MD, and Thomas Smith, MD, “SustainedEffectiveness of 10 kHz High-Frequency Spinal Cord Stimulation forPatients with Chronic, Low Back Pain: 24-Month Results of a ProspectiveMulticenter Study”, Pain Medicine, 2014, 15: 347-354; the disclosures ofwhich are incorporated herein by reference.

Another approach to pain management through SCS uses a stimulationtechnique called burst stimulation. In implementation of burststimulation therapy, packets (e.g., “bursts”) of high-frequency impulsesare delivered periodically (e.g., five pulses at 500 Hz, delivered 40times per second) at a current intensity below the paresthesiathreshold. It has been found that such burst stimulation suppressesneuropathic pain at least as well as, and possibly better than,traditional tonic SCS stimulation and provides such pain relief withouteliciting paresthesia. Burst stimulation that bypasses the paresthesiaprocess is hypothesized to have a different mechanism of action thanthat of traditional tonic SCS stimulation, and therefore may bypass Aβfiber activation (see e.g., Arie et al., “High frequency stimulation ofdorsal column axons: potential underlying mechanism of paresthesia-freeneuropathic pain”, incorporated by reference above; Beurrier, et al.,“Subthalamic nucleus neurons switch from single-spike activity toburst-firing mode,” J. Neurosci., 19(2): 599-609, 1999; and Stefan Schu,MD, PhD, Philipp J. Slotty, MD, Gregor Bara, MD, Monika von Knop,Deborah Edgar, PhDt, Jan Vesper, MD, PhD, “A Prospective, Randomised,Double-blind, Placebo-controlled Study to Examine the Effectiveness ofBurst Spinal Cord Stimulation Patterns for the Treatment of Failed BackSurgery Syndrome”, Neuromodulation 2014; 17: 443-450; the disclosures ofwhich are incorporated herein by reference.

Irrespective of the particular SCS stimulation technique implemented,stimuli amplitude (e.g., current intensity) and/or delivered charge areconventionally maintained below a comfort threshold, above whichrecruitment of Aβ fibers may be at a level so large as to producediscomfort and even pain in the patient, in order to provide comfortableoperation for a patient. Correspondingly, stimuli amplitude and/ordelivered charge are generally maintained above a recruitment thresholdto recruit desired action potentials for providing effective therapy tothe patient (e.g., inducing an analgesic effect whereby the patientexperiences no pain, or a relatively small amount of pain, at the regionof interest). Additionally, in accordance with burst stimulationtechniques, stimuli amplitude and/or delivered charge are maintainedbelow a paresthesia threshold.

Maintaining neural recruitment at an appropriate level for effectivenessof SCS and related neurostimulation therapies can be challenging due tovarious events, such as electrode migration and/or postural changes ofthe patient, that can alter the neural recruitment with respect to aparticular stimulus. For example, there is room in the epidural spacefor an electrode array to move, whereby such movement of the electrodesmay alter a distance between the electrode and one or more fibersresulting in changes to the recruitment efficacy of a particularstimulus. Additionally, the spinal cord itself may move within thecerebrospinal fluid (CSF) with respect to the dura, such as due topostural changes of the patient, whereby the distance and/or the amountof CSF between the spinal cord and the electrodes may change resultingin changes to the recruitment efficacy of a particular stimulus.

Measurement of evoked compound action potentials (ECAPs) provides ameans of directly assessing the level of fiber recruitment in the dorsalcolumns of the spinal cord. ECAPs are signals elicited by electricalstimulations and recorded near a bundle of fibers. In particular, ECAPsusually arrive less than one millisecond (<1 ms) after a correspondingstimulation pulse and last in the range of approximately one half to onemillisecond (0.5-1 ms). ECAPs may be measured and analyzed, for example,to evaluate and/or control the comfort and efficacy of a SCS treatmentregimen (see e.g., US patent publication numbers 2020/0282208 A1entitled “Neural Stimulation Dosing”; 2011/018448 A1 entitled “SpinalCord Stimulation to Treat Pain”; and 2020/0391031 A1 entitled “Systemand Method to Managing Stimulation of Select A-Beta Fiber Components”;the disclosures of which are incorporated herein by reference).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows an example stimulation system as may utilize embodimentsof sensing signal stimulation of embodiments of the present invention.

FIGS. 1B and 1C show an environment in which stimulation systemsimplementing sensing signal stimulation of embodiments of the presentinvention may be deployed.

FIG. 2 shows a functional block diagram of an example implantable pulsegenerator adapted to elicit sensing signals according to embodiments ofthe present invention.

FIG. 3 shows a graph representing a burst stimulation waveform of aparesthesia-free stimulation technique.

FIG. 4 shows a flow diagram of operation according to an example processto elicit sensing signals in association with corresponding therapeuticneural stimuli according to embodiments of the present invention.

FIGS. 5-9 show graphs representing interleaved implementations ofpinging-pulses delivered in association with therapeutic neural stimuliaccording to embodiments of the present invention.

FIGS. 10-12 show graphs representing postfixed implementations ofpinging-pulses delivered in association with therapeutic neural stimuliaccording to embodiments of the present invention.

FIG. 13 shows a flow diagram of operation according to an exampleprocess in which sensing signals elicited by pinging-pulses are utilizedin an open-loop implementation for configuration of a therapeuticstimulation regimen according to embodiments of the present invention.

FIG. 14 shows a flow diagram of operation according to an exampleprocess in which sensing signals elicited by pinging-pulses are utilizedin a closed-loop implementation for configuration of a therapeuticstimulation regimen according to embodiments of the present invention.

FIG. 15 depicts a graph representing interleaved implementations ofpinging-pulses delivered in association with therapeutic neural stimuliaccording to embodiments of the present invention.

FIG. 16 depicts a flowchart for processing sensor data to isolate ECAPfeatures for a neurostimulation therapy according to some embodiments.

FIGS. 17A-17B depict a waveform representing sensed electrical activitycorresponding to an electrical pulse and its evoked compound actionpotential for processing according to some embodiments.

FIGS. 18A-19B depict respective graphs of sensor data in thefrequency-temporal domain according to some embodiments.

FIGS. 20A-20B depicts isolated ECAP features with surrounding areasmasked with Gaussian noise according to some embodiments.

FIG. 21 depicts raw signal data obtain by sensing circuitry of an IPGand a graph represents processing for a reconstructed signal thatrepresents the segmented ECAP features according to some embodiments.

FIGS. 22A-22C depict ECAP and stimulation artifact signals and FIG. 23depicts a patient system computational model to allow recovery of ECAPfeatures from a sensing electrode according to some embodiments.

FIG. 24 depicts operations for conducting ECAP sensing operations for aneurostimulation system according to some representative embodiments.

FIG. 25 depicts an ECAP display according to some embodiments.

FIG. 26 depicts an exemplary clinician user interface for display ofECAP data to assist an implant procedure according to some embodiments.

FIGS. 27A-27B depict the propagation of ECAP from stimulation electrodesoccurring rostrally along respective recording electrodes along thedepicted stimulation lead for processing according to some embodiments.

FIGS. 28A-28C depict aspects of a phase shift or latency change forprocessing according to some embodiments.

FIGS. 29A-29B depict aspects of the emergence and/or disappearance of asecondary phase of the ECAPs according to some embodiments.

FIGS. 30A-30C depict aspects of the disappearance of a phase (P1) ofECAPs signal according to some embodiments.

FIG. 31 depicts lead arrangements where the ECAP is generated by theactivation of the dorsal column axons and the axonal activation ismaximized when the electric field is aligned in the axonal directionaccording to some embodiments.

DETAILED DESCRIPTION OF THE INVENTION

Sensing signal stimulation techniques are provided according toembodiments of the invention for use in sensing responsive signals withrespect to the application of paresthesia-free stimulation. For example,sensing signal initiators may be utilized with respect to implantablemedical devices operable to controllably deliver electrical pulses orsignals to targeted tissue or nerves after implantation of therespective device within a patient.

In the case of spinal cord stimulation (SCS), fibers that generateevoked compound action potentials (ECAPs) are generally the A-beta (Aβ)fibers located in the dorsal column. Accordingly, conventionalmeasurement of ECAPs may be practical with respect to traditional tonicSCS, where stimulation of the Aβ fibers is performed at levelssufficient to induce paresthesia. For example, conventional ECAP sensingis known to measure the direct stimulation response to conventionaltonic SCS to maintain a substantially constant level of paresthesia.However, the ECAPs for burst stimulation and high frequency stimulationmay occur at sufficiently low levels that the ECAPs are not sufficientto provide an accurate assessment of the concurrent neural response. Forexample, burst stimulation may be provided at sufficiently lowamplitudes to ensure that the patient does not experience paresthesiaand thereby the resulting ECAPs do not generate an electrical field ofsufficient strength for sensing using one or more electrodes of thestimulation lead. In these situations, ECAPs may not be present or maybe of such low signal strength and/or present in a very low signal tonoise ratio (SNR) so as to make their measurement and/or analysisimpractical or even impossible.

To aid in understanding concepts herein, the description that followsdescribes examples relating to implantable medical devices of a spinalcord stimulation (SCS) system. However, it is to be understood that,while sensing signal stimulation techniques in accordance with conceptsherein are well suited for applications in SCS, the disclosure in itsbroadest aspects is not so limited. Rather, sensing signal stimulationtechniques of the disclosure may be used with various types ofelectronic stimulus delivery systems.

Sensing signal stimulation according to concepts herein may be utilizedwith one or more therapy delivery elements comprising an electrical leadincluding one or more electrodes to deliver pulses or signals to arespective target tissue site in a patient and one or more sensingelectrodes to sense electrical signals at the target tissue site withinthe patient. In the various embodiments contemplated by this disclosure,therapy may include stimulation therapy, sensing or monitoring of one ormore physiological parameters, and/or the like. A target tissue site mayrefer generally to the target site for implantation of a therapydelivery element, regardless of the type of therapy. The target tissuemay, for example, be neural tissue of the spinal cord, dorsal root, ordorsal root ganglion in accordance with some embodiments. In accordancewith some examples, one or more respective electrodes in an electrodearray of an electrical lead may perform functions of both signaldelivery and signal sensing.

FIG. 1A illustrates a generalized neurostimulation system (NS) 10 thatmay be used in SCS, as well as other stimulation applications, thatgenerates electrical pulses for application to target tissue of thepatient. NS 10 generally includes implantable pulse generator 12,implantable lead 14, which carries an array of electrodes 18 (shownexaggerated for purposes of illustration), and optional implantableextension lead 16. Although only one lead 14 is shown, often two or moreleads are used with electronic stimulus delivery systems (e.g., as shownin FIG. 1C), such as for implementing a multi-stim set in which thepulse generator rapidly switches between multiple stimulation programsproviding stimulation pulses to the different leads.

Lead 14 includes elongated body 40 having proximal end 36 and distal end44. Elongated body 40 typically has a diameter of between about 0.03inches to 0.07 inches and a length within the range of 30 cm to 90 cmfor spinal cord stimulation applications. Elongated body 40 may becomposed of a suitable electrically insulative material, such as apolymer (e.g., polyurethane or silicone), and may be extruded as aunibody construction.

In the illustrated embodiment, proximal end 36 of lead 14 iselectrically coupled to distal end 38 of extension lead 16 via aconnector 20, typically associated with the extension lead 16. Proximalend 42 of extension lead 16 is electrically coupled to implantable pulsegenerator 12 via connector assembly 22 associated with housing 28.Alternatively, proximal end 36 of lead 14 can be electrically coupleddirectly to connector 20.

In the illustrated embodiment, implantable pulse generator 12 includeselectronic subassembly 24 (shown schematically), which includes controland pulse generation circuitry (not shown) for delivering electricalstimulation energy to electrodes 18 of lead 14 in a controlled manner.Implantable pulse generator 12 of the illustrated embodiment furtherincludes a power supply, such as battery 26.

Implantable pulse generator 12 provides a programmable stimulationsignal (e.g., in the form of electrical pulses or substantiallycontinuous-time signals) that is delivered to target stimulation sitesby electrodes 18. In applications with more than one lead 14,implantable pulse generator 12 may provide the same or a differentsignal to electrodes 18 of the therapy delivery elements.

In accordance with some embodiments, implantable pulse generator 12 cantake the form of an implantable receiver-stimulator in which the powersource for powering the implanted receiver, as well as control circuitryto command the receiver-stimulator, are contained in an externalcontroller inductively coupled to the receiver-stimulator via aninductive link. In still another embodiment, implantable pulse generator12 can take the form of an external trial stimulator (ETS), which hassimilar pulse generation circuitry as an implantable pulse generator(IPG), but differs in that it is a non-implantable device that is usedon a trial basis after lead 14 has been implanted and prior toimplantation of the IPG, to test the responsiveness of the stimulationthat is to be provided.

Housing 28 is composed of a biocompatible material, such as for exampletitanium, and forms a hermetically sealed compartment containingelectronic subassembly 24 and battery 26 is protected from the bodytissue and fluids. Connector assembly 22 is disposed in a portion ofhousing 28 that is, at least initially, not sealed. Connector assembly22 carries a plurality of contacts that are electrically coupled withrespective terminals at proximal ends of lead 14 or extension lead 16.Electrical conductors extend from connector assembly 22 and connect toelectronic subassembly 24.

FIG. 1B illustrates lead 14 implanted in epidural space 30 of a patientin close proximity to the dura, the outer layer that surrounds spinalcord 32, to deliver the intended therapeutic effects of spinal cordelectrical stimulation. The target stimulation sites may be anywherealong spinal cord 32. The target sites may, for example, includecervical, thoracic, lumbar, and sacral vertebral levels.

Because of the lack of space near lead exit point 34 where lead 14 exitsthe spinal column, implantable pulse generator 12 is generally implantedin a surgically-made pocket either in the abdomen or above the buttocks,such as illustrated in FIG. 1C. Implantable pulse generator 12 may, ofcourse, also be implanted in other locations of the patient's body. Useof extension lead 16 facilitates locating implantable pulse generator 12away from lead exit point 34. In some embodiments, extension lead 16serves as a lead adapter if proximal end 36 of lead 14 is not compatiblewith connector assembly 22 of implantable pulse generator 12, sincedifferent manufacturers use different connectors at the ends of theirstimulation leads and are not always compatible with connector assembly22.

As illustrated in FIG. 1C, NS 10 also may include clinician programmer46 and patient programmer 48. Clinician programmer 46 may be a handheldcomputing device that permits a clinician to program neurostimulationtherapy for patient using input keys and a display. For example, usingclinician programmer 46, the clinician may specify neurostimulationparameters for use in delivery of neurostimulation therapy. Clinicianprogrammer 46 supports telemetry (e.g., radio frequency telemetry) withimplantable pulse generator 12 to download neurostimulation parametersand, optionally, upload operational or physiological data stored byimplantable pulse generator 12. In this manner, the clinician mayperiodically interrogate implantable pulse generator 12 to evaluateefficacy and, if necessary, modify the stimulation parameters.

Similar to clinician programmer 46, patient programmer 48 may be ahandheld computing device. Patient programmer 48 may also include adisplay and input keys to allow patient to interact with patientprogrammer 48 and implantable pulse generator 12. Patient programmer 48provides a patient with an interface for control of neurostimulationtherapy provided by implantable pulse generator 12. For example, apatient may use patient programmer 48 to start, stop or adjustneurostimulation therapy. In particular, patient programmer 48 maypermit a patient to adjust stimulation parameters such as duration,amplitude, pulse width and pulse rate, within an adjustment rangespecified by the clinician via clinician programmer 46, or select from alibrary of stored stimulation therapy programs.

Implantable pulse generator 12, clinician programmer 46, and patientprogrammer 48 may communicate via cables or a wireless communication.Clinician programmer 46 and patient programmer 48 may, for example,communicate via wireless communication with implantable pulse generator12 using radio frequency (RF) telemetry techniques known in the art.Clinician programmer 46 and patient programmer 48 also may communicatewith each other using any of a variety of local wireless communicationtechniques, such as RF communication according to the 802.11 orBLUETOOTH specification sets, infrared communication (e.g., according tothe IrDA standard), or other standard or proprietary telemetryprotocols.

Since implantable pulse generator 12 is located remotely from targetlocation 49 for therapy, lead 14 and/or extension leads 16 is typicallyrouted through pathways subcutaneously formed along the torso of thepatient to a subcutaneous pocket where implantable pulse generator 12 islocated. As used hereinafter, “lead” and “lead extension” are usedinterchangeably, unless content clearly dictates otherwise.

Leads are typically fixed in place near the location selected by theclinician using one or more anchors 47, such as in the epidural space30. Anchor 47 can be positioned on lead 14 in a wide variety oflocations and orientations to accommodate individual anatomicaldifferences and the preferences of the clinician. Anchor 47 may then beaffixed to tissue using fasteners, such as for example, one or moresutures, staples, screws, or other fixation devices. The tissue to whichanchor 47 is affixed may include subcutaneous fascia layer, bone, orsome other type of tissue. Securing anchor 47 to tissue in this mannerprevents or reduces the chance that lead 14 will become dislodged orwill migrate in an undesired manner.

NS 10 may be operated to controllably deliver electrical pulses orsignals to targeted tissue or nerves within a patient, such as for thetreatment of one or more indications. Additionally, NS 10 may beoperated to sense and/or analyze signals responsive to the electronicstimuli, such as to inform fiber recruitment, to implement closed-loopfeedback control of electrical pulse delivery, etc. Accordingly,electronic subassembly 24 of implantable pulse generator 12 may includeprocessors, electronics devices, hardware devices, electronicscomponents, logical circuits, memories, software codes, firmware codes,etc., or any combination thereof configured for controlled stimulationand/or sensing operation. One or more functional blocks of electronicsubassembly 24 may, for example, be implemented as discrete gate ortransistor logic, discrete hardware components, or combinations thereofconfigured to provide logic for performing the functions describedherein. Additionally or alternatively, when implemented in software, oneor more functional blocks of electronic subassembly 24, or some portionthereof, may comprise code segments (e.g., one or more instruction sets,program code, programs, applications, etc.) operable upon a processor(e.g., a processing unit having computer readable media, such as asemiconductor memory device, a read only memory (ROM), a flash memory,an erasable ROM (EROM), etc., storing instructions which when executedperform functionality described herein) to provide logic for preformingthe functions described herein. Processors utilized in implementingfunctions herein may, for example, comprise a general-purpose processor,a digital signal processor (DSP), an application specific integratedcircuit (ASIC), a field programmable gate array (FPGA), or combinationsthereof.

An example embodiment of implantable pulse generator 12 is illustratedin the block diagram of FIG. 2 , wherein further details of exemplaryelectronic subassembly 24 are shown. Electronic subassembly 24 is shownin the example of FIG. 2 as being in communication with connectorassembly 22 and battery 26, which may operate as described above withreference to FIGS. 1A-1C. Electronic subassembly 24 is further shown asincluding processor 241 in communication with wireless radio 242 andmemory 243.

Wireless radio 242 may of embodiments may operate to facilitate wirelesscommunication between implantable pulse generator 12 and one or moredevices external thereto. For example, clinician programmer 46 and/orpatient programmer 48 (FIG. 1C) may communicate with implantable pulsegenerator 12 via wireless radio 242. Wireless radio 242 may comprise anRF transceiver operable according to one or more wireless communicationprotocols (e.g., the 802.11 or BLUETOOTH specification sets, otherstandard or proprietary telemetry protocols, etc.).

Memory 243 of the example embodiment is operable to store various codesegments executable by processor 241 to perform functions describedherein. In particular, the code segments of the example in FIG. 2includes stimulation control logic 231, sensing signal initiator logic232, and sensed signal analysis logic 233. Stimulation control logic 231may, for example, provide logic which when executed by processor 241controls delivery of stimulation pulses to neural tissue via output ofconnector assembly 22 to lead 14 (FIGS. 1A-1C) according to aparesthesia-free stimulation regimen (e.g., high-frequency spinal cordstimulation (HFSCS) or burst stimulation), a conventional stimulationregimen, etc. Sensing signal initiator logic 232 of embodiments provideslogic which when executed by processor 241 facilitates sensingresponsive signals with respect to the application of the stimuli, suchas through controlling operation to evoke responsive signals suitablefor measurement and/or analysis. Sensed signal analysis logic 233 may,for example, provide logic which when executed by processor is operativeto control sensing of signals, processing of sensed signals, analysis ofsensed signals, and/or delivery of information (e.g., to stimulationcontrol logic 231 executed by processor 241) regarding sensed signals.Memory 243 of embodiments may store code segments additionally oralternatively to those of the illustrated embodiment. For example,although not shown in the example of FIG. 2 , memory 243 may storecommunication logic operable to control communication betweenimplantable pulse generator 12 and one or more external systems (e.g.,clinician programmer 46 and/or patient programmer 48), such as forreceiving control signals and program code, transmitting data andtelemetry, etc.

As described in further detail below, sensing signal initiator logic 232of embodiments may operate to evoke responsive signals with sufficientsignal strength and/or signal to noise (S/N) characteristics to reliablyfacilitate their measurement and/or analysis, even in situations wherestimulation control logic 231 provides stimulation operation inaccordance with a paresthesia-free stimulation regimen (e.g., HFSCS orburst stimulation). Sensed signal analysis logic 233 may thus be enabledto sense responsive signals having suitable characteristics forfacilitating further processing and/or analysis, such as for informingfiber recruitment, providing information for closed-loop feedbackcontrol of the stimulus regimen by stimulation control logic 231, etc.

To aid in understanding concepts of the present invention facilitatingoperation as described above, examples with respect to implantable pulsegenerator 12 providing a burst stimulation regimen for SCS will bedescribed. It should be appreciated, however, that concepts of thepresent invention may be applied with respect to various forms ofparesthesia-free electrical stimulation (e.g., HFSCS, burst stimulation,high density stimulation, paresthesia-free noise stimulation, etc.)and/or for a variety of target areas (e.g., SCS, dorsal rootstimulation, and dorsal root ganglion stimulation). For example, sensingsignal stimulation according to some examples may be implemented withrespect to a stimulation regimen which defines a high frequencystimulation pattern that is controlled with a duty cycle havingon-periods and off-periods of stimulation, wherein sensing signalstimulation pinging-pulses are provided in association with off-cyclesof the high frequency stimulation pattern.

In operation according to an exemplary embodiment, implantable pulsegenerator 12 may implement a burst stimulation therapy to suppressesneuropathic pain without eliciting paresthesia (e.g., paresthesia-freestimulation). In operation according to a burst stimulation regimen,packets (e.g., “bursts”) of high-frequency impulses are deliveredperiodically at a current intensity below the paresthesia threshold. Forexample, a burst stimulation waveform may include five pulses ofcathodic pulses (or anodic pulses at the anode) with 1000 μs pulse widtheach, as shown in FIG. 3 (wherein only a single burst is shown as burst301). In a specific example, the frequency within the burst or pulserate (the “intra-burst frequency”) may be set to be 500 Hz, such as forSCS applications. Other intra-burst frequencies may be employedaccording to some embodiments to optimize therapy for a given patient.Continuing with the specific example, the frequency at which the burstsrepeat (the “inter-burst frequency”) may be nominally set to be 40 Hz,such as for SCS applications, and may be adjusted based on userpreference and applications. It should be understood, however, thatother intra-burst frequencies and/or inter-burst frequencies may beused, whether for SCS or other applications (e.g., the intra-burstfrequency and/or nominal inter-burst frequency may be adjusted fordorsal root ganglion (DRG) stimulation).

In operation of implantable pulse generator 12, one or more signals(“responsive signals”) generated or otherwise present in response to theelectrical stimulation pulses may be sensed, such as for use inanalyzing fiber recruitment, adjusting or otherwise controlling one ormore aspect of the burst stimulation regimen, etc. An evoked neuralresponse may, for example, be constituted of evoked compound actionpotentials. Evoked compound action potentials (ECAPs) are an example ofresponsive signals which may be sensed, processed, analyzed, and/or usedin providing closed-loop feedback according to embodiments of theinvention.

ECAPs are signals evoked by electrical stimulations and recorded near abundle of fibers. ECAPs usually arrive less than 1 ms (<1 ms) after acorresponding stimulation pulse and last in the range of approximatelyone half to one millisecond (0.5-1 ms). In the case of SCS, the fibersthat generate ECAPs are sensory fibers located in the dorsal column.With enough populational activation, sensory Aβ fibers also induceparesthesia, and therefore are the primary fibers responsible for themechanism of action for traditional tonic SCS (e.g., generatingparesthesia from Aβ fibers to mask pain). ECAPs may be measured andanalyzed, for example, to evaluate and/or control the comfort andefficacy of a SCS treatment regimen. However, ECAPs or similarlygenerated responsive signals having signal strength, signal to noiseratio (SNR), and/or other characteristics for their reliable measurementand analysis may not be present in some situations. For example, burststimulation at clinical amplitudes may not activate a sufficient numberof dorsal column fibers, and thus usually results in no measurable or nomeaningful ECAP data from sensor circuitry of the SCS IPG.

One potential solution to sensing ECAPs with respect to aparesthesia-free stimulation technique such as burst stimulation may beto increase the amplitude of the stimulation pulses of theparesthesia-free stimulation regime to beyond the level for perceptionand/or for generating paresthesia (e.g., burst stimulation pulses withamplitudes higher than 1.8 mA). Although this solution may be suitablein situations such as asleep implant procedures where patients do nothave to experience the sensation with high stimulation pulse amplitudes,it is not well suited for general use of an implantable pulse generatorto treat chronic pain of a patient. For example, the use of suchincreased amplitude of the pulses of otherwise paresthesia-freestimulation therapy to thereby increase the quality of the ECAPmeasurement and control process, would significantly reduce thepatient's experience and relief of pain to the paresthesia-freestimulation therapy—essentially eliminating the paresthesia-free natureof the stimulation and likely modifying the mechanism of action.

Some embodiments of the invention utilize sensing signal initiator logic232 in association with implementation of paresthesia-free stimulationby stimulation control logic 231 to implement sensing signal stimulationevoking responsive signals suitable for measurement and/or analysis bysensed signal analysis logic 233 without substantially changing thepatient's paresthesia-free therapy into a paresthesia-based therapy. Inoperation according to some examples, sensing signal initiator logic 232when executed by processor 241 may facilitate sensing of ECAPs inassociation with implementation of burst stimulation operating toprovide paresthesia-free stimulation. Sensing signal initiator logic 232of embodiments of the invention may, for example, control implantablepulse generator 12 to deliver one or more non-therapeutic pulses(“pinging-pulses”) configured for evoking responsive signals (e.g.,ECAPs) suitable for measurement and/or analysis in association with theapplication of neural stimuli. In operation of sensing signal initiatorlogic implementing sensing signal stimulation of embodiments of theinvention, pinging-pulses are provided for eliciting ECAPs and/or otherresponsive signals with respect to paresthesia-free stimulation (e.g.,burst stimulation or high frequency stimulation) substantially withouteliciting paresthesia either by the pinging-pulses or the therapeuticstimulation. For example, aspects of a pinging-pulse (e.g., currentintensity amplitude, pulse width, etc.) and/or pinging-pulse duty cycle(e.g., frequency of pinging-pulses, aggregate current intensityamplitude(s), aggregate pulse width(s), etc.) may be configured to avoideliciting paresthesia in a patient.

FIG. 4 shows an example flow according to a process operable to evokeresponsive signals suitable for measurement and/or analysis inassociation with the application of therapeutic neural stimuli inaccordance with concepts of the present disclosure. That is, flow 400shown in FIG. 4 provides a process to evoke sensing signals inassociation with corresponding therapeutic neural stimuli. The functionsof flow 400 shown in FIG. 4 may, for example, be performed by anembodiment of implantable pulse generator 12, such as through operationof processor 241 executing stimulation control logic 231, sensing signalinitiator logic 232, sensed signal analysis logic 233, and/or otherlogic for performing functions as described.

At block 401 of exemplary flow 400, pulses of a therapeutic stimulusregimen are delivered by implantable pulse generator 12, such as totarget tissue within a patient via electrodes 18 of lead 14. Forexample, processor 241 may execute stimulation control logic 231 toprovide and control delivery of the pulses of the therapeutic stimulusregimen. The amplitudes of the pulses of the therapeutic pulses of thestimulation regimen may be constant or may vary, such as according tothe treatment being delivered, the particular patient being treated,etc.

The therapeutic stimulus regimen may comprise one or more aparesthesia-free stimulation regimen (e.g., high-frequency stimulationor burst stimulation), etc. In accordance with some examples, thetherapeutic stimulus regimen may comprise a paresthesia-free stimulationregimen which itself results in no ECAPs or results in ECAPs of such lowsignal strength and/or SNR as to make their measurement and/or analysisimpractical or even impossible. As a specific example, the therapeuticstimulus regimen may delivery a burst stimulation configuration ofpulses, such as shown in the example of FIG. 3 .

Flow 400 of the illustrated embodiment is operable to evoke responsivesignals suitable for measurement and/or analysis in association with theapplication of the therapeutic stimulus regimen. Accordingly, at block402, one or more pinging-pulses are delivered by implantable pulsegenerator 12, such as to the target tissue within the patient viaelectrodes 18 of lead 14. For example, processor 241 may execute sensingsignal initiator logic 232 to provide and control delivery of thepinging-pulses of the sensing signal stimulation. Pinging-pulsesutilized to initiate sensing signals of embodiments of the inventioncomprise non-therapeutic configured for evoking responsive signalssuitable for measurement and/or analysis in association with thetherapeutic stimulus regimen. Pinging-pulses may, for example, beprovided for facilitating sensing ECAPs in association with operation ofa paresthesia-free stimulation technique. According to some examples,the pinging-pulses may be provided for eliciting ECAPs with respect toburst stimulation, without eliciting paresthesia either by thepinging-pulses or the burst stimulation. In operation according toembodiments, the IPG (e.g., sensed signal analysis logic 233) maymonitor a signal quality (e.g., a SNR) of the evoked neural response andcontrol an amplitude level of the pinging-pulses in response to thequality level of the evoked neural response.

In operation at block 402 of embodiments of the invention, sensingsignal initiator logic 232 may provide for an interleaved implementationto introduce the one or more pinging-pulses in between groups of pulsesof the therapeutic stimulus regimen (e.g. between burst groups of aburst stimulation regimen, during a pause of appropriate durationbetween instances of a high frequency tonic stimulation regimen, etc.).The pinging-pulses of an interleaved implementation may, for example,comprise monophasic cathodic pulses, biphasic charge-balanced cathodicpulses (e.g., with passive or active discharge), anodic-leading activelycharge-balanced pulses, or any combination thereof.

FIG. 5 shows an example of a pinging-pulse (e.g., a cathodic pulse withpassive discharge) interleaved with respect to bursts of a burststimulation regimen. In particular, pinging-pulse 511 is shown providedwithin between bursts of a burst stimulation regimen (only burst 501being shown, and it being understood that another burst having the sameor different burst stimulation waveform precedes pinging-pulse 511 inthe example timeline). Burst 501 may, for example, comprise a burststimulation waveform corresponding to that of FIG. 3 described above. Inoperation of an interleaved pinging-pulse implementation of someexamples, measuring an evoked neural response in a patient in responseto the pinging-pulses occurs without including an evoked neural responseto therapeutic pulses of the stimulation program

Pinging-pulses of embodiments of an interleaved implementation areconfigured to evoke responsive signals (e.g., sensing signals) suitablefor measurement and/or analysis in association with the therapeuticstimulus regimen without eliciting paresthesia. For example, variousaspects of a pinging-pulse, such as one or more of pulse width,amplitude, latency between the pinging-pulse and therapeutic pulses,active discharge pulse width, anodic-leading pulse width, etc., may beselected for evoking a sensing signal without eliciting paresthesia.

According to some embodiments of an interleaved implementation ofpinging-pulses, the cathodic phase of a pinging-pulse is controlled tobe in the range of 60-1000 μs in pulse width (e.g., 60 μs≤PP_(W)≤1000μs). The amplitude of the cathodic phase is selected and/or adjusted inoperation according to embodiments such that a single pinging-pulseevokes one or more sensing signals (e.g., eliciting ECAPs in the dorsalcolumn in the case of SCS). In some examples, the pinging-pulseamplitude is selected in the range of 0.5-5 mA (e.g., 0.5 mA≤PP_(A)≤5mA). The pinging-pulse amplitude may, for example, be selected in partbased upon various aspects of the particular implementation, such aspinging-pulse width, implant location, etc. A pinging-pulse trailinglatency of at least 1.2 ms (e.g., PP_(TL)≥1.2 ms) is provided between apinging-pulse of an interleaved implementation of embodiments and thesubsequent therapeutic pulses (e.g., the pulses of burst 501), such asto facilitate sufficient time for sensing responsive signals (e.g.,ECAPs). A pinging-pulse leading latency may be based upon theintra-burst frequency of the therapeutic pulses, the pinging-pulsetrailing latency, and the pinging-pulse pulse width.

Pinging-pulses of embodiments of an interleaved implementation may notbe present at every interval between therapeutic pulses (e.g., apinging-pulse may not be delivered in every inter-burst-interval wherebythe frequency or duty cycle of the pinging-pulses is less than theinter-burst rate of the burst stimulation pattern). In accordance withsome examples, the IPG generates the pinging-pulses at a frequency orduty cycle that is selected to be sufficiently low to prevent thepinging-pulses from generating paresthesia in the patient at anamplitude level selected to evoke a neural response for measurement bythe IPG. For example, some embodiments of the invention may distributethe occurrences of pinging-pulse (e.g., maintaining theinter-pinging-pulse frequency at low rate, such as 20 Hz or lower) inorder to avoid or minimize resulting paresthesia. The frequency ofoccurrence of the pinging-pulses may be set by a clinician during aprogramming process to verify the pinging-pulses do not generateparesthesia in a given patient according to some embodiments.

According to some embodiments of an interleaved implementation ofpinging-pulses, a pinging-pulse may be provided with active discharge.FIG. 6 shows an example of a pinging-pulse with active dischargeinserted between burst stimulation pulses (the preceding burst of whichis not visible in the graph of FIG. 6 ). In the example of FIG. 6 ,pinging-pulse 611 includes cathodic phase 611 a and anodic phase 611 b(e.g., generating pairs of pulses in sequence for the pinging-pulsesthat have opposite polarity), wherein anodic phase 611 b provides activedischarge with respect to cathodic phase 611 a. In operation accordingto embodiments in which a pinging-pulse is actively discharged, theactive discharge phase (e.g., anodic phase 611 b in the example of FIG.6 ) preferably matches the pulse width of the leading phase of thepinging-pulse (e.g., cathodic phase 611 a in the example of FIG. 6 ).

Although the foregoing examples of interleaved pinging-pulses have beenwith reference to pinging-pulse instances having a cathodic leadingphase, it should be appreciated that pinging-pulses having an anodicleading phase may be utilized in addition to or in the alternative topinging-pulses having a cathodic leading phase. FIG. 7 shows an exampleof an anodic-leading pinging-pulse with active discharge was insertedbetween burst stimulation pulses (the preceding burst of which is notvisible in the graph of FIG. 7 ). In the example of FIG. 7 ,pinging-pulse 711 includes anodic phase 711 a and cathodic phase 711 b,wherein cathodic phase 711 b provides active discharge with respect toanodic phase 711 a. When a pinging-pulse is implemented with ananodic-leading pulse according to some embodiments of the invention, theanodic pulse width may range from 500-1000 μs (e.g., 500μs≤PP_(APW)≤1000 μs), and the cathodic pulse width is preferably lessthan 200 μs (e.g., PP_(CPW)<200 μs). Such a configuration of anodicleading pinging-pulse may facilitate the cathodic phase elicitingsensing signals (e.g., responsive signals in the form of ECAPs)following the anodic phase. In operation according to embodiments of ananodic leading pinging-pulse configuration, the anodic phase provides apreconditioning pulse that increases the excitability of Aβ fibers, andthe trailing cathodic pulse has higher amplitude than anodic phasepulse. The anodic and cathodic pulses can be charge balanced or slightedcharge imbalanced (e.g., the charge resulting from the amplitude andpulse width of the pinging-pulse anodic phase is equal to orapproximately equal to the charge resulting from the amplitude and pulsewidth of the pinging-pulse cathodic phase).

The pinging-pulses of a sequence of pinging-pulses of an interleavedimplementation may each be configured the same or one or more may beconfigured differently. For example, interleaved pinging-pulses may beprovided in an implementation in which the pinging-pulses switch betweencathodal and anodal within a stimulation train. FIG. 8 shows an exampleof a pulse train in which pinging-pulses of alternating polarity areprovided. In particular, pinging-pulse 811 of the example comprises acathodic monophasic pulse, whereas pinging-pulse 812 comprises an anodicmonophasic pulse. Such an implementation is particularly well suited forimplementing monophasic pinging-pulses because the alternating pulsescancel each other. Alternating the polarity of pinging-pulses, such asshown in the example of FIG. 8 , may be utilized according toembodiments of the invention to improve the SNR of elicited sensingsignals. For example, the alternation in polarity may be utilized toimprove the SNR of ECAPs because the opposite polarity of stim pulsescan be added to zero, and the ECAPS themselves can be averaged. Such aninterleaved implementation of pinging-pulses with alternating polarityallows the use of a single pulse train to improve ECAP SNR, rather thantwo separate pulse trains with flipped polarity of electrodes to summateto improve ECAP SNR (e.g., conducting a summation operation of therespective evoked neural response to both pulses in sequence of oppositepolarity to increase signal-to-noise ratio), and therefore may reduceexperimenting time by half. Additionally, the frequency of the pingingpulses may be adjusted. For example, the frequency may be controlledsuch that only one pinging pulses is provided between bursts for someembodiments. Lower frequency pinging pulses may be applied such that apinging pulses are not generated before every burst but only for asubset of bursts in the overall waveform pattern. Alternatively, higherfrequencies may be selected for the pinging pulses may be selected suchthat more than one pining pulse is provided between consecutive burstsof pulses for other embodiments.

Interleaved implementations of pinging-pulses may be utilized withmulti-stim sets according to embodiments of the invention. For example,interleaved pinging-pulses may be implemented via a multi-stim set inwhich the implantable pulse generator operates to rapidly switch betweentwo programs of opposite polarity between electrodes. FIG. 9 shows anexample of a multi-stim pulse train of two electrodes in whichpinging-pulses of alternating polarities are interleaved. In particular,pinging-pulses 911 and 912 of alternating polarities in the illustratedexample are interleaved in the pulse train of a first electrode andpinging-pulses 913 and 914 of alternating polarities in the example areinterleaved in the pulse train of a second electrode. In addition to thepinging-pulses alternating in polarity, the therapeutic pulse groupsthemselves are also alternated in polarity.

In addition or in alternative to providing for an interleavedpinging-pulse implementation, operation at block 402 of embodiments ofthe invention may include sensing signal initiator logic 232 providingfor a postfixed implementation to introduce the one or morepinging-pulses with respect to pulses of the therapeutic stimulusregimen (e.g. appended to burst groups of a burst stimulation regimen,appended to a pulse train of a high frequency tonic stimulation regimen,etc.). The pinging-pulses of a postfixed implementation may, forexample, comprise pulse configurations based upon or corresponding topulses of the therapeutic stimulus regimen.

FIG. 10 shows an example of a pinging-pulse (e.g., an anodiccharge-balanced active discharge pulse) appended or postfixed to a groupof therapeutic pulses. In particular, burst 1001 of a burst stimulationregimen is shown as modified to include pinging-pulse 1011 optimized foreliciting sensing signals (e.g., ECAPs). In accordance with someexamples, the last passive discharge phase of a burst stimulationwaveform of the burst stimulation regimen may be replaced with apinging-pulse of embodiments of the invention. In the example of FIG. 10, an otherwise last passive discharge phase of burst 1001 has beenreplaced with pinging-pulse 1011 providing an active charge-balancinganodic pulse. Burst 1001 may, for example, comprise a modified burststimulation waveform corresponding to that of FIG. 3 described above,wherein the first four bursts should have properties of the burststimulation waveform of burst 301 and the last pulse of the burstcomprises a cathodic pulse followed by an anodic pulse. Accordingly, thelast passive discharge of the burst stimulation waveform of burst 301 isreplaced by an active discharge in an example of burst 1001.

Pinging-pulses of embodiments of a postfixed implementation areconfigured to evoke responsive signals (e.g., sensing signals) suitablefor measurement and/or analysis in association with the therapeuticstimulus regimen without eliciting paresthesia. For example, variousaspects of a pinging-pulse, such as one or more of pulse width,amplitude, correspondence to therapeutic pulse train, etc., may beselected for invoking a sensing signal without eliciting paresthesia.

According to embodiments of a postfixed implementation ofpinging-pulses, the amplitude (PP_(A)) of the anodic phase of apinging-pulse provided with respect to a burst may be determined bycalculating the total remaining charge of previous full burst groups,and dividing the charge by the pulse width of the anodic pulse. Thepinging-pulse amplitude (e.g., anodic phase amplitude) of embodimentsmay range from 3 to 50 times the amplitude of the therapeuticstimulation pulse (e.g., cathodic phase amplitude), such as dependingupon the impedance of the electrode-tissue interface and the anodicpulse width (e.g., PP_(A) may range from 3(SP_(A)) to 5(SP_(A))). Inaccordance with embodiments of a postfixed implementation, thepinging-pulse amplitude may be capped at the discomfort amplitude (e.g.,PP_(A)<a comfort threshold) so that the patient does not feeldiscomfort.

Pinging-pulses of postfixed implementations of embodiments of theinvention may comprise relatively small pulse widths (e.g., 100 μs pulsewidth, as compared to a more common 1000 μs pulse width of a therapeuticstimulation pulse). In accordance with some embodiments, the amplitudeof pinging-pulses having a small pulse width may be correspondinglycapped to ensure safety. In the use of such small pulse widthpinging-pulses having capped amplitudes, charge may remain that is notcompletely balanced. Accordingly, the implantable pulse generator may,according to some embodiments, proceed to discharge the remainingcharges with passive discharge. FIG. 11 shows burst 1101 of a postfixedimplementation for eliciting sensing signals (e.g., ECAPs), wherein thelast passive discharge phase of the burst has been replaced withpinging-pulse 1111 comprising an active charge-balancing anodic pulsehaving a small pulse width. As shown in FIG. 11 , the anodic pulse widthof pinging-pulse 1111 is small, and the amplitude is capped, wherebypassive discharge is used to discharge remaining charges. In operationaccording to some embodiments, a delay (e.g., trailing latency) of atleast 1.2 ms (e.g., PP_(TL)≥1.2 ms) may be provided between thepinging-pulse and the passive discharge to facilitate sensing ofresponsive signals (e.g., ECAPs).

According to embodiments of a postfixed implementation ofpinging-pulses, an active pulse may be provided to balance out thecharges. For example, another anodic pulse of equal amplitude to that ofthe cathodic burst pulses may be added after the anodic pulse of apostfixed pinging-pulse. The pulse width of such as charge balancingactive pulse may be calculated based on a duration to completely orsubstantially balance out the remaining charge. According to someexamples, a trailing latency (e.g., PP_(TL)≥1.2 ms) may be providedfollowing the pinging-pulse and before initiation of the chargebalancing active pulse, such as to facilitate sensing of responsivesignals (e.g., ECAPs). FIG. 12 shows burst 1201 of a postfixedimplementation for eliciting sensing signals (e.g., ECAPs), wherein thelast passive discharge phase of the burst has been replaced withpinging-pulse 1211 comprising an active charge-balancing anodic pulsehaving a small pulse width. As shown in FIG. 12 , the anodic pulse widthof pinging-pulse 1211 is small, and the amplitude is capped, wherebycharge balancing pulse 1221 is used to implemented to balance out thecharge (e.g., following a latency delay, PP_(TL)).

In other embodiments, the first pulse of a burst in a stimulationpattern may be modified to promote ECAP sensing. As shown in FIG. 15 ,waveform pattern 1500 includes multiple bursts of pulses generated insuccession including burst 1501. As shown, burst 1501 (and other burstin the pattern) includes a delay between the first pulse and the secondpulse that is longer than the delay between other pulses in burst 1501.This longer delay facilitates the sensing of the ECAP response to thefirst pulse of burst 1501. The delay between the first pulse and thesecond pulse may be a programmable setting to optimize ECAP sensing fora specific patient (either by clinician programming or automatically bysensing circuitry and ECAP signal analysis). The implementation of burst1501 differs from the use of tonic pinging pulses in that no passivedischarge occurs between the first pulse of burst 1501 and the secondpulse of 1502. In some embodiments, the amplitude and/or pulse width ofthe first pulse may also be increased or modified to facilitate thesensing of the ECAP response thereto.

Pinging-pulses of embodiments of a postfixed implementation may not bepresent with respect to every group of therapeutic pulses (e.g., apinging-pulse may not be delivered in every inter-burst-interval). Inaccordance with some examples, the IPG may generate the pinging-pulsesat a frequency or duty cycle that is selected to be sufficiently low toprevent the pinging-pulses from generating paresthesia in the patient atan amplitude level selected to evoke a neural response for measurementby the IPG For example, embodiments of the invention may distribute theoccurrences of pinging-pulse (e.g., maintaining the inter-pinging-pulsefrequency at low rate, such as 20 Hz or lower) in order to avoid orminimize resulting paresthesia. The frequency of the pinging-pulses maybe set by a clinician during a programming procedure to verify that thepinging-pulses do not elicit paresthesia in a given patient.

Postfixed implementations of pinging-pulses may be utilized withmulti-stim sets according to embodiments of the invention. For example,similar to the interleaved pinging-pulses implemented with respect tothe multi-stim pulse train of FIG. 9 discussed above, postfixedpinging-pulses of alternating polarities may be implemented with respectto a multi-stim pulse train of two electrodes according to embodiments.

Having described examples of operation at block 402 of FIG. 4 to evokeresponsive signals suitable for measurement and/or analysis inassociation with the application of the therapeutic stimulus regimen,and continuing with the description of flow 400, one or more responsivesignals may be sensed at block 403. For example, sensing signals (e.g.,ECAPs) elicited by a pinging-pulse (e.g., an instance of an interleavedpinging-pulse or a postfixed pinging-pulse) may be monitored, received,etc. by implantable pulse generator 12, such as via electrodes 18 oflead 14. In operation according to embodiments, processor 241 mayexecute sensed signal analysis logic 233 for monitoring sensing signalspresent in response to a pinging-pulse delivered by the implantablepulse generator.

Sensing signals monitored according to embodiments of the invention maybe utilized in a number of ways. For example, sensed signal analysislogic 233 of embodiments may perform processing of sensing signalselicited by pinging-pulses to derive various attributes of the monitoredsensing signals, such as for providing to a user (e.g., clinician),determining fiber recruitment, implementing changes to a correspondingtherapeutic stimulation regimen, etc.

FIG. 13 shows an example process in which sensing signals elicited bypinging-pulses of an embodiment of the invention are utilized in anopen-loop implementation for configuration of a therapeutic stimulationregimen. Block 1301 of flow 1300 shown in FIG. 13 comprises a process toelicit sensing signals in association with corresponding therapeuticneural stimuli corresponding to embodiments of flow 400 described above.

As an example of operation at block 1301 of some embodiments, SCS may beprovided to a patient using an IPG. The operation of this example mayinclude selecting one or more parameters for a stimulation program forSCS to provide electrical pulses to the patient without generatingparesthesia in the patient. The selecting may comprise selecting a firstamplitude value to control respective pulse amplitudes of therapeuticpulses of the stimulation program. The operation may also includegenerating, by the IPG, electrical pulses for the stimulation programaccording to the one or more parameters, and generating, by the IPG,pinging-pulses at amplitudes greater than pulse amplitudes of thetherapeutic pulses of the stimulation program. The pinging-pulses may beinterleaved with therapeutic pulses of the stimulation program. Theoperation may further include applying the electrical pulses generatedfor the stimulation program and the pinging-pulses to neural tissue ofthe spinal cord without generating paresthesia in the patient, andmeasuring an evoked neural response in the patient in response to thepinging-pulses.

In another example of operation at block 1301 of some embodiments, SCSmay be provided to a patient using an IPG. The operation of this examplemay include selecting one or more parameters for a stimulation programfor SCS to provide electrical pulses to the patient without generatingparesthesia in the patient. The operation may also include generating,by the IPG, electrical pulses for the stimulation program according tothe one or more parameters. The generating electrical pulses for thestimulation program may comprise modifying a pulse amplitude of selectedpulses for the stimulation program by increasing the pulse amplitude toa level for accurate measurement of a neural response by the IPG. Theselected pulses may, for example, constitute twenty percent or less of atotal number of pulses generated for the stimulation program. Theoperation may further include applying the electrical pulses generatedfor the stimulation program to neural tissue of the spinal cord withoutgenerating paresthesia in the patient, and measuring, by the IPG, anevoked neural response in the patient in response to pulses ofstimulation program with increased pulse amplitude for accuratemeasurement by the IPG.

At block 1302 of the example embodiment, monitored sensing signals areprocessed for obtaining various information useful with respect toconfiguration/reconfiguration of a corresponding therapeutic stimulationregimen. For example, sensed signal analysis logic 233 of embodimentsmay analyze one or more sensing signals (e.g., ECAPs) to determinewhether the energy content in various frequency clusters of a sensingsignal is within an acceptable range (e.g., performing thresholdanalysis using one or more thresholds, such as a recruitment threshold,comfort threshold, paresthesia threshold, etc., representing a selectedneural stimuli profile).

Correspondingly, at block 1303, sensing signal information resultingfrom the monitoring and processing of sensing signals may be output bythe implantable pulse generator. For example, sensed signal analysislogic 233 may utilize wireless radio 242 to communicate variousinformation with respect to one or more sensing signal, such asinformation indicating aspects of the effect of the stimulus regimen(e.g., that no pain or an acceptable low level of pain is experienced bythe patient, that no paresthesia or an acceptably low level ofparesthesia is experienced by the patient, etc.), to an external device(e.g., clinician programmer 46 of FIG. 1C).

At block 1304 of the illustrated embodiment, updated therapeuticstimulation information is received by the implantable pulse generatorand the therapeutic stimulation regimen updated accordingly. Forexample, a clinician may refer to the sensing signal information formaking one or more adjustments to neural stimuli of the therapeuticstimulation regimen, such as using clinician programmer 46. Thereafter,updated therapeutic stimulation information comprising the adjustmentsmay be provided to stimulation control logic 231 via wireless radio 242such that stimulation control logic 231 may reconfigure the therapeuticstimulation regimen and implement a thusly updated therapeuticstimulation regimen.

FIG. 14 shows an example process in which sensing signals elicited bypinging-pulses of an embodiment of the invention are utilized in aclosed-loop implementation for configuration of a therapeuticstimulation regimen. Block 1401 of flow 1400 shown in FIG. 14 comprisesa process to elicit sensing signals in association with correspondingtherapeutic neural stimuli corresponding to embodiments of flow 400described above.

At block 1402 of the illustrated embodiment, monitored sensing signalsare processed for identifying candidate updated therapeutic stimulationwaveforms. For example, sensed signal analysis logic 233 of embodimentsmay provide processing to convert one or more sensing signals (e.g.,ECAPs) to the frequency domain (e.g., fast Fourier transform) andimplement various analysis techniques, such as frequency discrimination,profile analysis, etc., to derive activity data useful inconfiguring/reconfiguring one or more aspect of a correspondingtherapeutic stimulation regimen. In operation according to embodiments,sensed signal analysis logic 233 may analyze one or more features from amorphology of sensing signals over time, sum the occurrences of one ormore features that occur with respect to sensing signals over a periodof time, etc., for generating the activity data. Activity data generatedthrough analysis of the sensing signals may be used in determiningaspects of updated therapeutic stimulation waveforms.

Correspondingly, at block 1403, results of the processing and analysisof the sensing signals is utilized to revise one or more aspects of thetherapeutic stimulation regimen. For example, sensed signal analysislogic 233 may provide updated therapeutic stimulation information, suchas may be revised based upon activity data generated from the sensedsignals, to stimulation control logic 231. Operation according to flow1400 of some examples may thus detect a change in the evoked neuralresponse of the patient to the pinging-pulses and automatically adjustone or more parameters for the stimulation program (e.g., modifying anamplitude level for respective pulses generated for the stimulationprogram without generating paresthesia in the patient) in response todetecting the change. Accordingly, stimulation control logic 231 mayreconfigure the therapeutic stimulation regimen and implement theupdated therapeutic stimulation regimen (e.g., returning to block 1401).

As can be appreciated from the forgoing, sensing signal stimulationimplementations of embodiments of the invention evoke responsive signalswith sufficient signal strength and/or S/N characteristics to providesensing signals facilitate reliable measurement and/or analysis. Sensingsignal stimulation implementations of embodiments may, for example,reliably evoke sensing signals (e.g., ECAPs) using pinging-pulses inassociation with paresthesia-free stimulation (e.g., burst stimulation).

In addition to modification of waveforms and/or pulse patterns tofacilitate sensing of ECAPs, certain embodiments conduct otheroperations to facilitate ECAP sensing. These operations may be performedfor the waveform/pulse patterns discussed herein and may occur forparesthesia and non-paresthesia based therapies.

ECAPs typically happen several ms after the end of the stimulationdelivery. Stimulation artifact is a powerful voltage fluctuation duringrecording, and it takes some time to let the artifact to recover to thebaseline after the stimulation ends. Often, stimulation recovery willoverlap with the time window in which ECAPs signal appears, which makesthe data sensing and analysis of ECAPs very difficult. Previous attemptsto solve this problem use a pre-generated model to calculate thestimulation artifact recovery, and then subtract the model generatedartifact recovery from the recorded signal to extract the ECAPs(Pilitsis J, et al, 2021). The disadvantage, however, is that thestimulation artifact will be different from day to day or from subjectto subject, due to the movement of the recording electrodes in/on thebody. Accordingly, the use of a pre-generated model to compensate forstimulation artifact in ECAP data can offer limited value.

In some embodiments, a neurostimulation system converts ECAP data in thetime domain into some temporal-frequency domain signal. Then, temporaland frequency-based features are extracted to conduct signal denoising.After the feature extraction, the signal is converted back into timedomain to obtain the relevant ECAP signal without noise or artifact.These processing operations are adaptive to each individual recordingand there is no need to use pre-generated model. By employing processingoperations in this manner, neurostimulation systems are capable of moreaccurately determining the effect(s) of neurostimulation and, thereby,improving patient therapy.

FIG. 16 depicts operations of a neurostimulation system for sensing andapplying ECAP data according to some embodiments. In 1601, neuralactivity is sensed using suitable sensing circuitry of an implantablepulse generator (IPG). The sensing circuitry may include sensingcircuitry described in published literature and/or used in commercialneurostimulation devices or any later developed circuitry. For ECAPapplications, the sensed neural activity is neural activity that isevoked by neurostimulation. Referring to FIG. 17A, waveform 1701represents sensed electrical activity corresponding to an electricalpulse and its evoked compound action potential. Due to the timing of theelectrical pulse, recovery time, and the ECAP itself, the sensedwaveform detected by the sensing circuitry may contain these variouscomponents. The sensed data may be truncated to exclude samples thatinclude the stimulation artifact from the electrical pulse whileretaining the artifact recovery component. The artifact recovery and theECAP components in the sensed data of the truncated time window areprocessed as discussed herein to isolate the ECAP component for furtheroperations of the neurostimulation system.

In 1602 of FIG. 16 , the digital samples of the sensed waveform in thetime domain and within a relevant time window are converted to asuitable frequency-temporal domain. In some embodiments, the processingoperations to transform to a suitable frequency-temporal domain includeapplying the wavelet transform.

Wavelets are mathematical functions that process data into differentfrequency components, and then study each component with a resolutionmatched to its scale. Wavelet processing has advantages over traditionalFourier methods in analyzing physical situations where the signalcontains discontinuities and sharp spikes. In contrast to the varietiesof Fourier analysis that appropriate observed data than the sines andcosines functions, wavelet analysis employs approximating functions thatare contained neatly in finite domains. The windowed Fourier transform(WFT) is a known application of representing the nonperiodic signal in afrequency-temporal domain. With the WFT, the input signal f(t) (in thiscase the sensed data samples containing the stimulation artifact, theartifact recovery, and the ECAP) is segmented or divided into sectionsor time windows, and each section/time window is analyzed for itsfrequency content separately. If the signal has sharp transitions, theinput data may be windowed so that the sections converge to zero at theendpoints. This windowing is accomplished via a weight function thatplaces less emphasis near the interval's endpoints than in the middle.The effect of the window is to localize the signal in time.

The processing operations of transforming signal into frequency-temporaldomain are not limited to wavelet transform but may also include methodsfor transforming signal into frequency or scales-like signal. Suchmethods might include Short Time Fourier Transform (STFT/DTFT), wavelettransform, Hilbert Transform, et al. according to other embodiments.

The processing of the time domain data into the frequency-temporaldomain generates a two-dimensional array of data. The two dimensions arefrequency and time. Each value in the two-dimensional array representsthe signal power/amplitude at a given frequency at a given time. Graph1702 represents a graph of the two-dimensional sensed data in thefrequency-temporal domain according to some embodiments.

The two-dimensional array of data is subjected to closed-contouranalysis and/or other segmentation processing to extract ECAP relatedfeatures in the data (1603 in FIG. 16 ). Specifically, the ECAPcomponent of the data is discernably as discrete phases at differenttemporal-frequency space locations. For example, the graph of FIG. 17Bincludes closed contours 1703, 1704, and 1705 which each correspond torespective phases of the ECAP response of the patient to the electricalpulses. FIGS. 18A-18B depict respective graphs of the same data in thefrequency-temporal domain in which a three-dimensional graph 1801 of theamplitude versus time and frequency is provided by projecting into agraph format, as shown in FIG. 18A. Upon ECAP feature identification,the longitudinal and time axis angle of each closed contour 1802, 1803may be extracted (as shown in FIG. 18A-B). The estimated time durationof each corresponding ECAP feature can be estimated from the identifiedclosed contour features in the frequency-temporal domain data.

2D signal segmentation techniques may be employed to extract theclosed-contours that contain relevant ECAP related data. Suitable signalsegmentation techniques include thresholding, clustering,histogram-based filtering, edge-detection, regional property-baseddetection, or machine-learning & computer vision-based methods. Both,semantic and instance segmentation methods, may be employed to identifyall contours and accurately classify them. Additionally, informationabout the contour shape is integrated to facilitate classification ofregions as signals of interest versus noise (ex: circularity,eccentricity, etc.).

After initial segmentation processing, we can further extract relatedfeatures to help further screening which features could be ECAPs signalor the targeted signal we are interested in. For example, extraction ofamplitude-based features, the angle between the longitudinal axis andthe time axis, the duration of the closed contour of the ECAPs likesignal, etc. These features can be used to compare to or measure againstknown features or profiles of ECAP signals, and then further rule outthose extracted features that are not ECAP-related or our target signalsof interest.

Referring to FIGS. 19A and 19B, graph 1901 depicts segmentation of thedifferent phases of the ECAP response of the patient to the electricalpulse with graph 1902 representing a 3-D graph of the frequencycoefficients from the segmented data. After segmentation, processing ofthe remaining data may occur. The frequency coefficients for eachsegmented feature may be resettled with the base of each feature beginset to zero. Additionally, the remaining data points in the 2-Dfrequency-temporal domain that are not associated with one of thesegmented ECAP features (i.e., zero data points) are masked withGaussian noise, as shown in graphs 2001 and 2002 of FIGS. 20A-20B.

Referring to FIG. 16 , the 2-D array of data in the frequency-temporaldomain corresponding to extracted ECAP features is converted back intotime domain. Any suitable transformation processing may be employed. Theconversion may include application of a 2D kernel to smooth the signaland then transformation of the data into a one dimensional time series.Alternatively, the conversion may include transformation of the datainto a one dimensional time series and then application of a 1D kernelto smooth the signal. Referring to FIG. 21 , graph 2101 represents rawsignal data obtain by sensing circuitry of an IPG and graph 2102represents processing of the signal as discussed herein to generate thereconstructed signal that represents the segmented ECAP features.

Referring again to FIG. 16 , in 1606, the reconstructed signal isanalyzed (as discussed herein) to determine whether any appropriationaction should be taken and, if so, the patient's neurostimulationtherapy is modified and/or an alert is provided to the patient and/orthe patient's clinician (1607).

The processing of ECAP data into a temporal-frequency domain may be usedfor any number of applications to assist neurostimulation therapies. Insome embodiments, this analysis is conducted while a clinician implantsone or more stimulation leads within a patient during a medicalprocedure. For example, the position of a stimulation lead is animportant factor for successful neurostimulation therapy. If thestimulation is incorrectly positioned, the proper dorsal fibers of thespinal cord may be stimulation by electrical pulses applied throughelectrodes of the lead. Alternatively, the electrical pulses maystimulation unwanted neural tissue causing unwanted side effects (e.g.,muscle stimulation or painful/uncomfortable sensory effects).

FIG. 25 depicts ECAP display 2501 according to some embodiments. As seenin display 2501, the ECAPs signal exhibits a complicated multiphasicmorphology (as compared to the morphology of the ECAP signal seen inFIGS. 17A-17B). ECAP display 2501 was created by stimulating, measuringthe patient response using a suitable electrode, and processing thesignal as discussed herein (including the processing operationsdescribed with respect to FIG. 16 ). The display of the morphology shownin ECAP display 2501 may indicate unexpected activation in response tothe stimulation (which might indicate the activation of muscleactivity). When such a response is seen by the clinician during animplant procedure, the clinician may reposition one or more thestimulation leads before completing the implant procedure with the leador leads in their final position.

Clinician user interface 2601 (in FIG. 26 ) depicts display of ECAP datato assist an implant procedure according to some embodiments. Clinicianuser interface 2601 may be provided using a clinician programming deviceas discussed herein using a clinician “app” on the device. Clinicianuser interface 2601 may display a medical image of the patient with theposition of the leads shown relative to the patient's anatomy. Themedical image may be a virtual construction for the position or a directimage from medical imaging technology (e.g., a fluoroscopic imagingsystem). Clinician user interface 2601 may display the electrode(s) usedfor stimulation and recording operations. Clinician user interface 2601may include a graphical user control element to switch to conventionalprogramming screens (to set stimulation settings, e.g., amplitude,frequency, pulse width, etc.). Clinician user interface 2601 depictsECAP data in the time domain and in the temporal/frequency domain asdiscussed herein as shown in ECAP display 2602. The implanting clinicianmay view ECAP display 2602 to ensure that the expected patient responseto the stimulation is obtained at the implant position.

In some embodiments, ECAP measurement and objective analysis will beconducted real time during an implant procedure. The ECAP results willbe displayed alongside the fluoroscopy image to provide guidance forphysicians during the implantation process. In some embodiments,clinician user interface 2601 may also provide a predicted patientreported outcome (“PRO”) based on the current signals that the system ismeasuring during implantation process. The predicted may be conducted bya mathematical model that is trained based on historical offline data.During the implantation process, the newly measured ECAP signal will befeed into the model, and a predicted PRO outcome in PRO graph 2603 willbe shown to inform physician about the effectiveness of the stimulationapplied to the patient. This predicted PRO, together with ECAPs signalvisualization, will be used to provide quantitative analysis real timeduring the implantation procedure.

The PRO could be any patient reported outcome data from historicalsessions from the same or other patients. The PRO data could consist ofany type of patient reported outcome including, but not limited to,patient reported score, quality of life assessment score, paresthesiainformation from historical session or during the session reported bythe patient, etc. The features used to train the model offline andconduct prediction during the actual implantation process could includeECAPs signal and its derived features, other types of physiological datarecorded during a implantation session, such as somatosensory evokedresponse, ECG, EEG, etc. The features might also use patient reportedresults to feed in as an input to the model, based on how the predictedPRO is defined.

In other embodiments, samples of sensed data in response to electricalpulses applied to the patient may be subjected to other processing toremove stimulation artifact recovery features from ECAP features in thesensed data. FIGS. 22A-22C depicts ECAP data related to stimulation oncaudal electrodes and sensed data using electrodes rostral to thestimulation electrodes. As shown in lead configuration 2201 in FIG. 22B,two percutaneous leads are implanted in the epidural space of thepatient. The electrodes of the two leads are roughly placed in a linear,sequential order. The percutaneous leads are placed such that the mostdistal electrode (“electrode 1”) of the first lead is immediately caudalto the most proximal electrode (“electrode 16”) of the secondstimulation. Electrodes 7 and 8 (with polarities of “−” and “+”) areused to apply stimulation pulses from the IPG to dorsal fibers of thepatient's spinal cord.

Now, because electrode 9 of the second stimulation lead has sufficientlyspatial separation from electrodes 7 and 8 of the first stimulationlead, it is possible to measure a clean ECAP signal. However, in channel3 which is located very close from the stimulation channels, onlyartifact contaminated signal can be measured in certain circumstances.The stimulation artifact and artifact recovery features propagate morerapidly than the ECAP features. For sensing electrodes closer to thestimulation electrodes, there is overlap of the respective features intime. With electrodes with greater separation, there is sufficienttemporal separation between features to allow ready identification ofthe separate features as represented in the timing graph 2203 of FIG.22C.

As shown in sensed data graphs 2202 of FIG. 22A, the ECAP featuresincluding the multiple positive phases (P1, P2, and P3) and negativephases (N1 and N2) are identifiable from the sensed data using electrode(or channel) 9. However, for electrode (channel) 3, the sensed data islargely dominated by the artifact/artifact recovery features from theapplied electrical pulse and, hence, the ECAP features are hidden in thesensed data from electrode 3.

As shown in FIG. 23 , a patient system computational model is created toallow recovery of ECAP features from a sensing electrode that isrelatively close to one or more stimulation electrodes. As seen incomputational relationships 2301 of FIG. 23 , the signal ofelectrode/channel 3 (that is contaminated by stimulationartifact/recovery features) is defined as the input of the patientsystem and the signal sensed by electrode/channel 9 (which has cleanECAP signal) is defined as the output of the system. The patient systemcan be represented as a transfer function. To perform systemidentification to find a transfer function model, a state-space model isdefined by matrices A, B, C and D. These matrices can be solved from theinput and output signals by utilizing the Eigensystem realizationalgorithm (ERA) may be applied. Upon determination of these matrices A,B, C, and D, the system is characterized and, then, can be applied tosubsequent data samples to obtain the ECAP features from a signalcontaminated with stimulation pulse artifact/recovery features. That is,using the state-space model, it is possible to estimate output yt (cleanECAP signal) from input ut (artifact contaminated signal).

FIG. 24 depicts operations for conducting ECAP sensing operations for aneurostimulation system according to some representative embodiments. In2401, neural activity in response to an electrical pulse is sensed usingcircuitry of IPG using two separate electrodes. In 2402, systemidentification operations are performed using the sensed data from thetwo electrodes. The system identification operations determine atransform function that transforms that time series data sensed usingthe first electrode into the time series data sensed using the secondelectrodes. In 2404, the transform function is applied to subsequentlysensed data to remove artifact and/or artifact recovery features fromthe sensed data. In 2405, the sensed data after application of thetransform function is analyzed using suitable ECAP analysis operations.In 2406, the neurostimulation therapy of the patient is modified and/oran alert is provided to the patient and/or the patient's clinician.

In some embodiments, ECAP analysis is applied to detect migration of oneor more stimulation leads after implantation into a patient. Thedetection of migration may detect relative movement of one stimulationrelative to another stimulation lead. In other embodiments, detection ofmigration of a stimulation lead may detect migration of a stimulationlead relative to an anatomical structure of the patient. In addition,the migration (in either case) may be transient. For example, theposition of the leads and/or their respective electrodes may changebased on patient posture and some embodiments detect such changes. Thedetected change may be used to infer patient posture, position,activity, and/or the like and stimulation may be modified asappropriate.

FIG. 27A-27B depict the propagation of ECAP from stimulation electrodesoccurring rostrally along respective recording electrodes along thedepicted stimulation lead. As shown in FIG. 27A, electrodes of channels5 and 6 (shown as Ch5 and Ch6) are used as a bipolar pair (one negativeand one positive electrode) for application of a stimulation pulse. Theelectrical pulse causes an ECAP and the ECAP propagates through theneural tissue. In this case, Ch1-Ch4 of the same stimulation lead andCh9-16 of a second stimulation lead positioned substantially paralleland rostrally to the first stimulation lead can be used to measure thepropagating ECAP The detected waveform including the ECAP is shown intime adjacent to each electrode of channel. Line 2702 shows thebeginning of the ECAP feature in time as detected by each respectiveelectrode or channel. Near the stimulation site (more caudally), theevoked response has shorter latency from the stimulation artifact, whileaway from the stimulation site (more rostrally), the evoked response haslonger latency from the stimulation artifact.

In some embodiments, the ECAP signal can be used to detect the relativeposition of multiple leads (e.g., two stimulation leads commonlyimplanted). Stimulation is initiated by one of the implanted leads andECAP neural recordings are recorded on the other lead. Across multiplecontacts of the leads, ECAPs signals will present different phase shiftor latency depends on the location (as shown in FIG. 28A).

FIGS. 28B-28C illustrate aspects of a phase shift or latency change forprocessing according to some embodiments are shown. The phase shift orlatency change could be viewed in both time domain in regular timeseries data, or it can be viewed in the transformed domain, as shown ingraph 2801 of FIG. 28B and in FIG. 28C, respectively. The example showsthe transformed domain as the scalogram of using wavelet transformapplied on the original time series recording. The methodology used insuch transform could also include any other similar signal processingmethods, such as Fourier Transform based methods (FFT, DTFT), HilbertTransform based methods (HHT), which can generate any spatial-temporal,frequency/scale-temporal signal map to visualize the latency change.

In one example, the latency of the ECAPs recording (as shown in FIGS.27A-27B) indicates the distance between the two leads. In this manner, adiagnostic can be run when the subject is known to be in a particularposition (e.g., lying down when sleeping) and the latency of the ECAPneural signal following the stimulation pulse, as indicated at 2702, maybe used to determine the relative position of the two leads in therostro-caudal direction. For example, given any contact on the recordinglead, if with decreasing latency at different time of measurements, therostral lead is moving more caudally or the caudal lead is moving morerostrally. Similarly, if the recorded ECAP signal is with increasinglatency at different measurement time, it is likely that the rostrallead is moving rostrally, or the caudal lead is moving more caudally.

In another embodiment of the multiple leads implanted, the emergenceand/or disappearance of a secondary phase of the ECAPs could happen asthe recording contact is moving towards the stimulation location (asshown graph 2901 in FIG. 29A and FIG. 29B). In the case of emergence ofnew phase of ECAPs signal for a given contact, it indicates the rostralrecording lead might moving more caudally, or the caudal stimulationlead is moving rostrally, as indicated at 2902. In the case of thedisappearance of the secondary phase of the ECAPs signal, it indicatesthat the rostral recording lead might move more rostrally, or the caudalstimulation lead might move more caudally.

Referring to FIGS. 30A-30C, aspects of the disappearance of a phase (P1)of ECAPs signal are shown. FIG. 30B shows a graph illustrating thedisappearance of the phase (P1) ECAPs signal. When two leads are movingtowards to each other, as shown at 3001 in FIG. 30A, either recordinglead is moving more rostrally, or stimulation leads is moving morecaudally. The first positive peak (P1) from the same recording channelis completely disappeared after the lead has moved. The data may beobserved in both time series (as in the graph of FIG. 30A) and scalogram(as shown in FIG. 30C).

As shown in the respective graphs, the timing of the phases (arrival,disappearance, etc.) can be identified in the time domain and/or in thetemporal/frequency domain. The various techniques discussed herein maybe applied to recorded data for the ECAP analysis.

The timing analysis discussed herein is not limited to application onthe ECAPs signal that is recorded after the stimulation delivery. In thecase of no ECAPs signal is being triggered, the waveform or itstransformation of the artifactual recording could also be used toconduct the time domain or transform domain analysis to track if thereis any signal latency or phase changes.

In other embodiments of multiple implanted leads, at least one electrodecontract from each lead is used to generate ECAPs. The ECAP is generatedby the activation of the dorsal column axons and the axonal activationis maximized when the electric field is aligned in the axonal direction(as shown in lead arrangements 3101 of FIG. 31 ). With lead migration,the angle between the electric field and the axonal direction changes,which results in the percentage of the activated axonal population andthe ECAP signal amplitude and morphology. Different stimulationamplitudes, configuration and recording configuration are used and themorphology profile of ECAP characteristics including the peak to peakvalue the shape of ECAPs and the latency is assessed. Differentconfiguration of differential recording can be also used. With migrationthe morphology of ECAP including the peak to peak value shape andlatency will be also affected. Combinations of different stimulationelectrode pairs and differential recording pairs are tried, and theprofiles of ECAP signals are recorded (which migration the ECAP profileswould alter). In addition to the change of the angle between theelectric field and the axonal direction, the change of the surroundingstructure of the stimulation and the recording lead will affect theprofile of the ECAPs with lead migration. The ECAP threshold amplitudewould change when the stimulation electrode contacts are under bonyvertebrae compared to inter-vertebral space. In addition to the changeof the angle between the electric field and the axonal direction, thechange of the distance between anode and cathode will affect theelectric field strength resulting in ECAP profile changes.

Although the present disclosure and its advantages have been describedin detail, it should be understood that various changes, substitutionsand alterations can be made herein without departing from the spirit andscope of the design as defined by the appended claims. Moreover, thescope of the present application is not intended to be limited to theparticular embodiments of the process, machine, manufacture, compositionof matter, means, methods and steps described in the specification. Asone of ordinary skill in the art will readily appreciate from thepresent disclosure, processes, machines, manufacture, compositions ofmatter, means, methods, or steps, presently existing or later to bedeveloped that perform substantially the same function or achievesubstantially the same result as the corresponding embodiments describedherein may be utilized according to the present disclosure. Accordingly,the appended claims are intended to include within their scope suchprocesses, machines, manufacture, compositions of matter, means,methods, or steps.

Moreover, the scope of the present application is not intended to belimited to the particular embodiments of the process, machine,manufacture, composition of matter, means, methods and steps describedin the specification.

What is claimed is:
 1. A method of providing a neurostimulation therapyto a patient using an implantable pulse generator (IPG), comprising:communicating a first signal from an external device to the IPG toprovide electrical stimulation to neural tissue of the patient;generating electrical pulses by the IPG in response to the first signal;applying the generated electrical pulses to neural tissue of the patientusing one or more electrodes of one or more stimulation leads; measuringneural response to the applied electrical pulses through one or moreelectrodes of one or more stimulation leads using sensing circuitry ofthe IPG; communicating data indicative of the measured neural responseto the external device from the IPG; processing the data indicative ofthe measured neural response into transformed data in a frequency andtime domain and isolating evoked compound action potential (ECAP)features in the neural response; and displaying a graph of the isolatedECAP features to a user of the external device for evaluation of theneurostimulation therapy.
 2. The method of claim 1 further comprising:displaying, on the external device, a representation of one or moreelectrodes used to apply electrical pulses and a representation of oneor more electrodes used to measure the neural response.
 3. The method ofclaim 1 further comprising: displaying representations of electrodesused to apply electrical pulses and to measure the neural response overa medical image of an implant region including the representedelectrodes.
 4. The method of claim 1 further comprising: processing oneor more isolated ECAP features to calculate ECAP amplitude of one ormore phases of an ECAP response.
 5. The method of claim 1 furthercomprising: processing one or more to calculate ECAP phase duration forone or more phases of an ECAP response.
 6. The method of claim 1 whereinthe graph is a two-dimensional representation of multiple ECAP phases.7. The method of claim 1 wherein the graph is a three-dimensionalrepresentation of multiple ECAP phases.
 8. The method of claim 1 whereinthe external device is adapted to isolate discrete phases an ECAPresponse.
 9. The method of claim 1 wherein the external device isadapted to detect morphology of ECAP features that differs from anexpected morphology to detect an undesired patient response toapplication of the generated electrical pulses.
 10. The method of claim1 wherein the external device is adapted to, after isolating ECAPfeatures in a frequency and time domain representation, transform dataindicative of the ECAP features into a one-dimensional time domain toform a reconstructed signal of ECAP values.
 11. A system for providing aneurostimulation therapy to a patient using an implantable pulsegenerator (IPG), comprising: an implantable pulse generator (IPG) forgenerating electrical pulses, wherein the IPG comprises sensingcircuitry for sensing neural activity of the patient in response toelectrical pulses; one or more stimulation leads with multipleelectrodes for applying electrical pulses to neural tissue of thepatient; and an external device adapted to wirelessly communicate withthe IPG when implanted in the patient, wherein the IPG is adapted tocommunicated data to the external device indicative of neural activityof the patient in response to one or more electrical pulses; and whereinthe external device is adapted (1) to communicate a first signal from anexternal device to the IPG to provide electrical stimulation to neuraltissue of the patient; (2) to receive data, from the IPG, indicative ofa measured neural response to one or more electrical pulses; (3) toprocess the data indicative of the measured neural response intotransformed data in a frequency and time domain and isolate evokedcompound action potential (ECAP) features in the neural response; and(4) to display a graph of the isolated ECAP features to a user of theexternal device for evaluation of the neurostimulation therapy.
 12. Thesystem of claim 11 wherein the external device is adapted to display arepresentation of one or more electrodes used to apply electrical pulsesand a representation of one or more electrodes used to measure theneural response.
 13. The system of claim 11 wherein the external devicesis adapted to display representations of electrodes used to applyelectrical pulses and to measure the neural response over a medicalimage of an implant region including the represented electrodes.
 14. Thesystem of claim 11 wherein the external devices is adapted to processone or more isolated ECAP features to calculate ECAP amplitude of one ormore phases of an ECAP response.
 15. The system of claim 11 wherein theexternal devices is adapted to process one or more to calculate ECAPphase duration for one or more phases of an ECAP response.
 16. Thesystem of claim 11 wherein the graph is a two-dimensional representationof multiple ECAP phases.
 17. The system of claim 1 wherein the graph isa three-dimensional representation of multiple ECAP phases.
 18. Thesystem of claim 11 wherein the external device is adapted to isolatediscrete phases an ECAP response.
 19. The system of claim 11 wherein theexternal device is adapted to detect morphology of ECAP features thatdiffers from an expected morphology to detect an undesired patientresponse to application of the generated electrical pulses.
 20. Thesystem of claim 11 wherein the external device is adapted to, afterisolating ECAP features in a frequency and time domain representation,transform data indicative of the ECAP features into a one-dimensionaltime domain to form a reconstructed signal of ECAP values.